Proteins, the epitome of molecular form and function, remain as the most challenging targets for design. Despite substantial advances in the design of "small-molecule" enzyme active site models, little progress has been mad toward the design and synthesis of "large-molecule" systems that can mimic both the structural as well as functional properties of natural enzymes. Here we propose new concepts, based on well-known physical organic principles, for the rational design of peptide-base catalysts with beta-keto acid decarboxylase and photooxidase activities. This work also attempts to further our understanding about the effects of protein micro environment and structure on electron transfer process and chemical catalysis. It is our hope that the knowledge gained from these studies would not only enhance our understanding about the workings of natural enzymes and contribute to the state of the art in protein design and synthesis, but also assist in the future designs of tailor-made catalysts with therapeutic as well as industrial applications. The research proposed here is founded on a new methodology , developed in our laboratory, for the design of requisite protein scaffolds-these findings have been disclosed in four recent publications. Additional preliminary experimental evidence in support of the proposed research is also provided in form of a) preliminary X-ray crystallographic data on the three-helix bundle metalloprotein, b) theoretical molecular modeling and electrostatic calculations pertinent to the design of the decarboxylase catalyst, c) a new methodology for the formation of RuII- bipyridyl alpha-helical peptides, and d) a novel chemoselective synthetic process for the template-assisted assembly of four-helix bundle metalloproteins-purposefully developed for the rational design of the photooxidase system. Here, we propose to extend our work on the artificial protein constructs toward the design of functional peptide- based catalysts. The specific aims of the proposed research are: I. To design, synthesize, and characterize an artificial Schiff base- mediated oxaloacetate decarboxylase by exploiting the effects of neighboring group electrostatic and charge-helix dipole interactions on the pKa of designated amino functionalities. II. To design, synthesize, and characterize a novel photooxidase catalyst by incorporating two active site moieties within the four-helix bundle protein-like scaffolding-an internal photo-induced reductase site made up of multiple ruthenium bipyridyl moieties, and a metalloporphyrin site for the designated oxygen activation and substrate oxidation.